Nanobubbles detect and destroy disease

HOUSTON and MINSK, Belarus – Tiny bubbles pack a punch, enough
to potentially knock out cancer. They also could be used for cancer diagnostics,
offering a tool to both detect and treat the disease. Those are some of the research
findings of a group from Rice University and the University of Texas M.D. Anderson
Center, both in Houston, and the A.V. Lykov Heat and Mass Transfer Institute in
Minsk, Belarus.

Research leader Dmitri O. Lapotko noted that the researchers demonstrated
what they call theranostics, a novel approach that combines diagnosis, therapy and
guidance of that therapy to specific cells or tissues. The aim is to do this on
the most fundamental level.

Lapotko, a physicist at Rice with an appointment at the institute,
said, “The goal is cell-level theranostics – future medicine that spots
and eliminates disease before it develops into a real threat.”

The scientists showed how this might work by using gold nanoparticles
and lasers to create tunable, transient plasmonic nanobubbles, which they generated
by exposing gold nanoparticles to the appropriate laser light. The plasmonic nanobubbles
thus produced form the basis for both diagnostics and treatment.
Gold nanoparticles taken into a cancer cell generate a nanobubble
and an accompanying signal when hit with a pump laser pulse. Increasing the laser
power produces a larger bubble, which mechanically damages the cell. Courtesy of
Dmitri Lapotko, Rice University.
In this scheme, the researchers target the nanoparticles at specific
cells by functionalizing them with conjugate antibodies. As a result, the gold nanoparticles
accumulate in those cells with specific characteristics, and the plasmonic nanobubbles
also are produced in those cells.

In a Feb. 26, 2010, Nanotechnology paper demonstrating this concept,
they reported using living lung cancer cells that expressed the epidermal growth
factor receptor. They coated 50-nm-diameter gold nanoparticles with an antibody
to that receptor and incubated them with the cells.

In their setup, they used a 0.5-ns, 532-nm laser pulse to generate
the plasmonic nanobubbles. They chose this wavelength because it was near the nanoparticles’
plasmon resonance peak, a point of maximum response that changes with particle size.

For bubble detection, they used a 0.5-ns, 690-nm probe laser to
do time-resolved optical scattering imaging. They delayed the probe anywhere from
1 to 10 ns behind the pump pulse, which allowed time for the bubbles to form and
so be detected without cell damage. For imaging, they used a CCD camera from Andor
Technology of Belfast, UK, with optics collecting the light from the sample and
sending it to the camera.

When continuous monitoring was required, they used a continuous
probe laser at 633 nm and a photodetector from Thorlabs of Newton, N.J. This arrangement
enabled them to gauge the lifetime of the bubbles, which is related to bubble size.
Bigger bubbles last longer – and they also do more damage. Thus, by tuning
the laser pulse energy used to generate the bubbles to a low level, the investigators
could have the bubbles merely highlight target cell location. At a higher level,
the bubbles would be larger, and the energy they released could damage or even destroy
cells.

The researchers showed that the plasmonic nanobubbles produced
a fiftyfold increase in scattering and, hence, detectability, as compared with the
signal from the nanoparticles alone. These bubbles also could destroy targeted cells
by various means, including by disrupting their membranes. Because the laser parameters
required for detection are quite different from those needed for destruction, one
possible extension of this setup would result in real-time adjustment and guidance
of plasmonic nanobubble theranostics at the cellular level.

As for the future, Lapotko noted that different-size particles
would allow the use of various laser wavelengths in the technique. He also said
that clinical applications based on the nanobubble approach are under development.
There have been some promising results that should be published soon, he said. “We
have generated plasmonic nanobubbles in vivo and were able to detect them without
any harm to a host.”